Down-regulation of circDMNT3B is conducive to intestinal mucosal permeability dysfunction of rats with sepsis via sponging miR-20b-5p.

Jiao Liu,Zhenliang Wen,Hangxiang Du,Tao Wang,Lidi Zhang,Yizhu Chen,Yongan Liu,Dechang Chen

doi:10.1111/jcmm.15324

Jiao Liu, Zhenliang Wen + Show 6 more

Open Access

https://doi.org/10.1111/jcmm.15324

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Abstract

Sepsis is a life‐threatening syndrome with a high risk of mortality, which is caused by the dysregulated host response to infection. We examined significant roles of circDMNT3B and miR‐20b‐5p in the intestinal mucosal permeability dysfunction of rats with sepsis. SD rats were randomly divided into 6 groups (n = 10/group): sham group, sepsis group, si‐negative control group, circDNMT3B‐si1 group, circDNMT3B‐si2 group and circDNMT3B‐si1 + anti‐miR‐20b‐5p group. The level of malondialdehyde (MDA) content, superoxide dismutase (SOD) activity, interleukin (IL)‐6 and IL‐10 levels were measured through ELISA assay kits. Cell survival rate and cell apoptosis were evaluated by Cell‐Counting Kit‐8 Assay and flow cytometry, respectively. Luciferase reporter assays were used to investigate interactions between miR‐20b‐5p circDMNT3B in HEK‐293T cells. Silencing circDNMT3B can significantly increase the level of d‐lactic acid, FD‐40, MDA, diamine oxidase, IL‐10 and IL‐6, compared with sepsis group, while the SOD activity was lower. Silencing circDNMT3B leads to oxidative damage and influence inflammatory factors level in intestinal tissue. CircDNMT3B was identified as a target gene of miR‐20b‐5p. Silencing circDNMT3B decreased cell survival and induced apoptosis in Caco2 cells treated with LPS, which was reversed by anti‐miR‐20b‐5p. MiR‐20b‐5p inhibitor remarkably down‐regulated mentioned‐above levels, in addition to up‐regulate SOD activity, which may relieve the damage of intestinal mucosal permeability caused by silencing circDNMT3B in sepsis rats. Down‐regulation of circDMNT3B was conducive to the dysfunction of intestinal mucosal permeability via sponging miR‐20b‐5p in sepsis rats, which may provide the novel strategy for sepsis treatment in the future.

Highlights

Sepsis, a global health issue, is caused by a dysregulated host response to infection with a high risk of mortality rate.[1]
We found that the down-regulation of circDMNT3B was conducive to intestinal mucosal permeability dysfunction of rats with sepsis via sponging miR-20b-5p
Our findings indicated that rats with sepsis showed higher levels of d-lactic acid, FD-40, MDA, Diamine oxidase (DAO), IL-10 and IL-6, compared with the sham group, but the superoxide dismutase (SOD) activity was decreased in sepsis rats

Summary

| INTRODUCTION

A global health issue, is caused by a dysregulated host response to infection with a high risk of mortality rate.[1]. MiRNAs, 19-25 nucleotides, are small non-coding RNAs that modulate post-transcriptional gene expression via targeting mRNAs.[5] Several miRNAs have been identified as potential biomarkers for the prognosis, diagnosis and treatment of sepsis.[6,7,8] MiR-20b-5p originates from the conservative paralogous miR-17-2∼363 cluster 9 and have been reported its significant role in regulating cell differentiation, proliferation and apoptosis.[10] Previous studies showed that miR-20b-5p was involved in the cell apoptosis, and the miR-20b-5p expression was significantly higher in the colorectal cancer group as compared to the normal group, which might be considered as a therapeutic biomarker.[11] to our knowledge, the possible mechanisms of miR-20b-5p in sepsis progression are still unclear. We have been suggested that circDNMT3B might be a target gene of miR-20b-5p and explored their significant role in the intestinal mucosal permeability dysfunction of rats with sepsis, aiming to provide important insights into the clinical diagnosis and treatment of sepsis

| METHODS

Findings

| DISCUSSION